Silencing of peroxiredoxin II by promoter methylation is necessary for the survival and migration of gastric cancer cells

Peroxiredoxin (Prx), a family of ubiquitous thiol peroxidases, functions as a redox signaling regulator that controls cellular Hâ‚‚Oâ‚‚ in mammalian cells and has recently received attention for being overexpressed in various cancer types. In this study, we show that Prx type II (PrxII) is rather silenced in gastric cancer cells. PrxII expression is severely downregulated in 9 out of the 28 gastric cancer cell lines. Strikingly, PrxII expression is completely lost in three cell lines, MKN28, MKN74 and SNU484. Loss of PrxII expression is due to DNA methyltransferase 1-dependent methylation at the promoter region of the PrxII gene. Restoration of PrxII expression using a retroviral system markedly reduces the colony-forming ability and migratory activity of both MKN28 and SNU484 cells by inhibiting Src kinase. Mechanistically, PrxII peroxidase activity is essential for regulating gastric cancer cell migration. Bioinformatics analysis from The Cancer Genome Atlas stomach cancer data (STAD) revealed significantly low PrxII expression in gastric cancer patients and a negative correlation between PrxII expression and methylation levels. More importantly, low PrxII expression also strongly correlates with poor survival in cancer patients. Thus our study suggests that PrxII may be the first thiol peroxidase that simultaneously regulates both survival and metastasis in gastric cancer cells with high clinical relevance.

Predictors of job satisfaction and burnout among tuberculosis management nurses and physicians / 한국역학회지

OBJECTIVES: This study examined job satisfaction, empowerment, job stress, and burnout among tuberculosis management nurses and physicians in public healthcare institutions. METHODS: This was a cross-sectional study analyzing survey data collected from 249 nurses and 57 physicians in 105 public health centers, three public tuberculosis hospitals, and one tertiary hospital. The survey questionnaire comprised general characteristics, work-related characteristics, and four index scales (job satisfaction, empowerment, job stress, and burnout). The two-sample t-test was used to estimate the mean differences in the four index scales. Multiple regression analysis was used to determine whether general and work-related characteristics affected the four index scales. RESULTS: The job satisfaction and empowerment scores of the nurses were lower than those of the physicians. Except for the tuberculosis-specialized hospitals alone, the average job satisfaction scores of nurses were higher than those of physicians. Moreover, the nurses reported more job stress and burnout than did the physicians in tuberculosis departments in public healthcare institutions in Korea; in particular, the burnout reported by nurses was significantly higher than that reported by physicians at the National Medical Center. Marital status, nursing position, number of coworkers, the average number of days of overtime work per month, self-rated health, and hospital type were associated with the four index scales. CONCLUSIONS: Overall, nurses were more vulnerable to job stress and burnout than physicians. Reducing the workload of nurses by ensuring the presence of sufficient nursing staff and equipment, as well as by equipping facilities to prevent tuberculosis infections, should be considered priorities.

A Cannabinoid Receptor Agonist N-Arachidonoyl Dopamine Inhibits Adipocyte Differentiation in Human Mesenchymal Stem Cells

Endocannabinoids can affect multiple cellular targets, such as cannabinoid (CB) receptors, transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and peroxisome proliferator-activated receptor gamma (PPARgamma). The stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene transcription of the CB1 receptor, TRPV1 and PPARgamma. In this study, the effects of three endocannabinoids, N-arachidonoyl ethanolamine (AEA), N-arachidonoyl dopamine (NADA) and 2-arachidonoyl glycerol (2-AG), on adipogenesis in hBM-MSCs were evaluated. The adipocyte differentiation was promoted by AEA whereas inhibited by NADA. No change was observed by the treatment of non-cytotoxic concentrations of 2-AG. The difference between AEA and NADA in the regulation of adipogenesis is associated with their effects on PPARgamma transactivation. AEA can directly activate PPARgamma. The effect of AEA on PPARgamma in hBM-MSCs may prevail over that on the CB1 receptor mediated signal transduction, giving rise to the AEA-induced promotion of adipogenesis. In contrast, NADA had no effect on the PPARgamma activity in the PPARgamma transactivation assay. The inhibitory effect of NADA on adipogenesis in hBM-MSCs was reversed not by capsazepine, a TRPV1 antagonist, but by rimonabant, a CB1 antagonist/inverse agonist. Rimonabant by itself promoted adipogenesis in hBM-MSCs, which may be interpreted as the result of the inverse agonism of the CB1 receptor. This result suggests that the constantly active CB1 receptor may contribute to suppress the adipocyte differentiation of hBM-MSCs. Therefore, the selective CB1 agonists that are unable to affect cellular PPARgamma activity inhibit adipogenesis in hBM-MSCs.